As highlighted by recent genome-wide analyses in diverse organisms and cell types, subcellular targeting of mRNAs has emerged as a major mechanism for cells to establish functionally distinct compartments and structures. For protein synthesis to be spatially restricted, translation of localizing mRNAs is silenced during their transport and is activated when they reach their final destination. Such a precise translation pattern is controlled by repressors, which are specifically recruited to transport ribonucleoprotein particles and block translation at different steps. Functional studies have revealed that the inactivation of these repressors, either by pre-localized proteins or in response to conserved signalling pathways, triggers local protein synthesis.

SummaryIntracellular targeting of mRNAs has long been recognized as a means to produce proteins locally, but has only recently emerged as a prevalent mechanism used by a wide variety of polarized cell types. Localization of mRNA molecules within the cytoplasm provides a basis for cell polarization, thus underlying developmental processes such as asymmetric cell division, cell migration, neuronal maturation and embryonic patterning. In this review, we describe and discuss recent advances in our understanding of both the regulation and functions of RNA localization during animal development.Key words: RNA localization, RNA transport, Local translation, Cell polarity, Post-transcriptional gene regulation Introduction Establishment of cell polarity is crucial for the execution of developmental programmes governing key processes, including specification of cell fates, individual or collective cell movements and specialization of somatic cell types. Cell polarization depends on the asymmetric segregation of organelles and various molecules within the cell. Polarized accumulation of RNA molecules was first visualized nearly 30 years ago, when -actin mRNA was found to be asymmetrically localized within ascidian eggs and embryos (Jeffery et al., 1983). Following this, the discovery of the first localized maternal mRNAs in Xenopus (Rebagliati et al., 1985) and Drosophila oocytes (Frigerio et al., 1986;Berleth et al., 1988) provided evidence for the earlier proposal that localized RNA determinants could be responsible for early embryonic patterning (Kandler-Singer and Kalthoff, 1976). mRNAs were soon found to be asymmetrically distributed within differentiated somatic cells, such as fibroblasts (Lawrence and Singer, 1986), oligodendrocytes (Trapp et al., 1987) and neurons (Garner et al., 1988), and to colocalize with their encoded proteins, establishing intracellular transport of mRNAs as a potential mechanism used to target the production of selected proteins to discrete sites.Significant improvements in RNA detection methods led to the identification of a growing number of localized mRNAs. Still, in the early 2000s, the set of described targeted mRNAs was limited to ~100 (reviewed by Bashirullah et al., 1998;Palacios and St Johnston, 2001) and the process of mRNA localization was thought to be restricted to specific cell types. However, recent genome-wide analyses (see Table 1) have changed this view dramatically, and strongly suggest that subcellular targeting of mRNAs is a prevalent mechanism used by polarized cells to establish functionally distinct compartments (Fig. 1). Particularly striking was the discovery that >70% of the 2314 expressed transcripts analysed in a highresolution in situ hybridization screen were subcellularly localized in Drosophila embryos (Lécuyer et al., 2007). Moreover, hundreds to thousands of mRNAs have been detected in cellular compartments as diverse as the mitotic apparatus (Blower et al., 2007;Sharp et al., 2011), pseudopodia (Mili et al., 2008), dendrites (Moccia et al., 2003;Poon et a...

Local translation of asymmetrically enriched mRNAs is a powerful mechanism for functional polarization of the cell. In Drosophila, exclusive accumulation of Oskar protein at the posterior pole of the oocyte is essential for development of the future embryo. This is achieved by the formation of a dynamic oskar ribonucleoprotein (RNP) complex regulating the transport of oskar mRNA, its translational repression while unlocalized, and its translational activation upon arrival at the posterior pole. We identified the nucleo-cytoplasmic shuttling protein PTB (polypyrimidine tract-binding protein)/hnRNP I as a new factor associating with the oskar RNP in vivo. While PTB function is largely dispensable for oskar mRNA transport, it is necessary for translational repression of the localizing mRNA. Unexpectedly, a cytoplasmic form of PTB can associate with oskar mRNA and repress its translation, suggesting that nuclear recruitment of PTB to oskar complexes is not required for its regulatory function. Furthermore, PTB binds directly to multiple sites along the oskar 39 untranslated region and mediates assembly of high-order complexes containing multiple oskar RNA molecules in vivo. Thus, PTB is a key structural component of oskar RNP complexes that dually controls formation of high-order RNP particles and translational silencing. In eukaryotic cells, transcription represents the first step of gene expression. However, a variety of nuclear and cytoplasmic post-transcriptional events determine the final fate of RNAs and thus regulate gene product diversity as well as the spatio-temporal pattern of gene expression.In recent years, subcellular targeting of mRNAs, coupled to localized translation, has emerged as a powerful mechanism to spatially and temporally restrict protein synthesis. Furthermore, a genome-wide in situ hybridization analysis in Drosophila embryos suggests that RNA localization could represent a general mechanism for the establishment of cell polarity (Lecuyer et al. 2007). Consistent with this, functional studies have shown that local translation of asymmetrically enriched mRNAs is used by differentiated cells to generate functionally distinct compartments, or by developing organisms to partition cell fate determinants (St Johnston 2005;Du et al. 2007). In several species, the asymmetric distribution in unfertilized eggs of maternal RNAs encoding cytoplasmic determinants controls embryonic body axis specification. In Drosophila, oskar mRNA encodes the posterior determinant and is transported to the posterior pole of the oocyte, where it is specifically translated. This precise spatio-temporal control is critical for embryonic patterning, as mutant oocytes in which oskar is not expressed at the posterior pole develop into embryos lacking abdominal structures and germ cells (Ephrussi et al. 1991;Kim-Ha et al. 1991). Conversely, ectopic translation of unlocalized oskar causes patterning defects characterized by a loss of anterior structures, and in extreme cases, duplication of posterior structures (Ephrussi and...